Janz S, Gawrisch K, Lester D S
Laboratory of Genetics, National Cancer Institute, NIH, Bethesda, Maryland 20892.
Cancer Res. 1995 Feb 1;55(3):518-24.
Pristane (2,6,10,14-tetramethylpentadecane) is a C19-isoalkane that promotes the development of plasmacytomas in genetically susceptible BALB/c mice. Similarities between the effects of pristane and protein kinase C (PKC)-activating phorbol esters suggested that the tumor promoting activity of pristane might involve the activation of PKC. Here we show that up to 5 mol% of pristane can be homogeneously incorporated into phosphatidylcholine/phosphatidylserine bilayers. Membrane-incorporated pristane partially activated PKC and increased phorbol ester binding to the bilayer by more than 50%. Pristane (50 microM) delivered as an inclusion complex with beta-cyclodextrin to promyelocytic HL-60 leukemia cells induced a partial long-term translocation of PKC to the cell membrane. This was accompanied by differentiation of HL-60 cells into macrophage-like cells. It is concluded that activation of PKC may comprise an important aspect of the tumor promoting potential of pristane.
降植烷（2,6,10,14-四甲基十五烷）是一种C19异烷烃，可促进基因易感的BALB/c小鼠浆细胞瘤的发展。降植烷与蛋白激酶C（PKC）激活佛波酯的作用相似，提示降植烷的促肿瘤活性可能涉及PKC的激活。在此我们表明，高达5摩尔%的降植烷可均匀掺入磷脂酰胆碱/磷脂酰丝氨酸双层膜中。膜结合的降植烷部分激活PKC，并使佛波酯与双层膜的结合增加50%以上。以β-环糊精包合物形式递送至早幼粒细胞HL-60白血病细胞的50微摩尔降植烷诱导PKC向细胞膜的部分长期转位。这伴随着HL-60细胞分化为巨噬细胞样细胞。得出的结论是，PKC的激活可能是降植烷促肿瘤潜力的一个重要方面。
